长链非编码RNA-SRA调控热休克蛋白Hsp70促进心肌肥厚的分子机制研究

心肌肥厚是导致心力衰竭的重要原因，但其机制尚未阐明。长链非编码RNA（lncRNA）的调控模式广泛且多样，是研究心肌肥厚机制的理想突破口。本项目前期研究发现：类固醇受体RNA激活因子SRA（一种lncRNA）在异丙肾上腺素诱导心肌肥厚的心脏组织中表达升高，而敲除心脏SRA后可下调心脏中Hsp70的表达及抑制Akt/Gsk3β信号通路，同时心肌肥厚程度显著减轻，这些结果提示SRA/Hsp70/Akt途径在促进心肌肥厚过程中发挥重要的作用。本课题将利用转基因鼠、腺病毒感染、RNA pull down、RNA结合蛋白免疫沉淀及ChIP-qPCR等技术，重点明确SRA在促进心肌肥厚过程中的作用，阐明其调控Hsp70表达而影响Akt信号通路的分子机制，以期为心肌肥厚的治疗提供新的靶标。

Cardiac hypertrophy is an important cause of heart failure, but its mechanism has not yet been elucidated. Due to the multiformity and universality in regulation modes, long non-coding RNAs (lncRNAs) become the breakthrough to explore mechanisms of cardiac hypertrophy. Our early research verified that: SRA (an lncRNA) was increased in isoproterenol-induced cardiac hypertrophy, while knockdown of cardiac SRA could suppress Hsp70 expression and the Akt / Gsk3β signaling pathway in the heart, at the same time myocardial hypertrophy was significant attenuated. These results suggest that the SRA / Hsp70 / Akt pathway may play an important role in myocardial hypertrophy development. This study will use transgenic mice, adenovirus infection, RNA pull down, RNA-binding protein immunoprecipitation and ChIP-qPCR to focus on the role of SRA in myocardial hypertrophy, and further clarify its role and molecular mechanism in regulating Hsp70 expression and affecting Akt signaling pathway, thus to provide a new target for the treatment of cardiac hypertrophy.